EFFECT OF NAPROXEN ON GASTROESOPHAGEAL REFLUX AND ESOPHAGEAL FUNCTION- A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY

Objectives: Gastrointestinal symptoms, particularly pyrosis, complicat e nonsteroidal anti-inflammatory drug (NSAID) use. NSAIDs cause esopha geal injury, and H-2, blockers are often prescribed for, and successfu lly control, NSAID-related symptoms. To determine whether NSAIDs can i nduce gastroesophageal reflux, we studied the effect of a commonly use d NSAID, naproxen, on reflux parameters and esophageal function. Metho ds: Nine healthy volunteers (five males, four females, age 23-34 yr) w ere studied. After basal measurements were taken, the subjects randoml y received naproxen 500 mg p.o. b.i.d. or placebo for 1 wk. On day 6, the subjects underwent esophageal manometry with a water-perfused syst em and Dent sleeve. Body pressures, contraction velocity, and duration of contraction were recorded in the distal 7 cm of the esophagus. The lower esophageal sphincter pressure (LESP) and number of transient re laxations (TLESRs) were monitored. This was followed by 24-h pH monito ring. The subjects then crossed over to the other drug after a minimum 14-day wash-out period. Results: No subject experienced any GI sympto ms during the study. One subject developed reflux-induced symptoms a f ew months after completing the study and was excluded from the analysi s. The total fraction of time (pH < 4) was 4.9 +/- 1.0% in the basal s tate, 5.5 +/- 1.4% on placebo, and 5.4 +/- 1.5% on naproxen. These dif ferences were not significant. The number of reflux episodes and the e sophageal clearance time were not affected by naproxen. The LESP in th e basal state was 32.1 +/- 5.6 mm Hg, 32.3 +/- 4.2 mm Hg on placebo, a nd 29.9 +/- 3.3 mm Hg on naproxen (p = NS). The number of TLESRs per 3 0 minutes in the basal state was 3.5 +/- 0.9, 4.6 +/- 1.2 on placebo, and 5.8 +/- 1.0 on naproxen (p = NS). The speed and duration of contra ctions were not affected by naproxen. The excluded subject had marked basal reflux (total fraction of time pH < 4 = 10.7%), low LESP (8 mm H g), and a marked increase in reflux on naproxen (total fraction of tim e pH < 4 = 53%). Conclusions: Naproxen did not induce reflux in normal subjects, although reflux did increase in some subjects. Naproxen had no significant effect on motility parameters. Our data suggest that N SAIDs do not impair the anti-reflux barrier or induce reflux. Pyrosis experienced during NSAID use may not arise from the esophagus or may r eflect altered esophageal sensitivity. A single subject with decreased LESP and asymptomatic increased acid exposure in the basal state had a marked increase in reflux on naproxen. This person subsequently deve loped symptomatic gastroesophageal reflux. The effect of NSAIDs on ind ividuals with a propensity to reflux: deserves further study.